This case describes a 60-year-old woman presenting with choreiform movements, weight loss, and dysarthria over the past 6 months. Imaging showed T1 hyperintensity in the basal ganglia. She tested positive for anti-CRMP-5 antibodies, which are associated with malignancy in over 90% of cases. Further workup revealed a small cell lung cancer. Her symptoms improved with cancer treatment and decreasing antibody levels, indicating this was a paraneoplastic neurological syndrome.

1. A 60-Year-Old Woman with Chorea and Weight Loss
J Gen Intern Med. 2012 Jun;27(6):747-51.
Amanda Vick, MD, Ryan R. Kraemer, MD, Jason L. Morris, MD, Lisa L. Willett, MD,
Robert M. Centor, MD, Carlos A. Estrada, MD, MS, and J. Martin Rodriguez, MD.
University of Alabama and Veterans Affairs Medical Center, Birmingham
DUAL PROCESS THEORY
JGIM EXERCISES IN CLINICAL REASONING
Teacher’s Guide:
Gabrielle Berger MD, Juan Lessing MD

2. Objectives
1. Define Dual Process Theory.
2. Describe the application of System 1 and System 2
thinking to clinical reasoning.

3. • Fast
• Implicit/automatic
• Draws on prior experience
• Based on pattern recognition
and mental shortcuts
System 1
Intuitive
• Slow
• Deliberate/rational
• Careful analysis to avoid
diagnostic errors in complex
cases
System 2
Analytic
Dual Process Theory
Acad Med. 2009; 84:1022-28.
Cognitive psychology framework adapted for
clinicians to organize complex information

4. Dual Process Theory
Experienced clinicians activate System 1 or System 2
thinking depending on clinical scenario
System 1
Intuitive
System 2
Analytic

5. The Case
Chief Complaint: abnormal movements and weight loss
HPI
A 60-year-old woman was transferred to tertiary care for
further evaluation of choreiform movements and weight
loss
For the past 6 months she endorsed:
• Progressive clumsiness and chorea
• Difficulty speaking and eating due to involuntary
movements of the mouth
• Intermittent progressive abdominal pain and nausea
• Documented unintentional weight loss (60lbs)

6. Discussion
What do you know/remember about chorea?
What diagnoses come to mind (System 1)?
What organizational approach would help you broaden
your differential diagnosis (System 2)?

7. Dual Process Theory
• Relatively quick
• Implicit, uses first impressions
• Based on pattern recognition
• Requires little cognitive effort
• Experienced clinicians use more often
System 1: The Intuitive Approach
Example:
“Common disorders associated with chorea are
Sydenham chorea and Huntington disease.”

8. Dual Process Theory
• Commonly used by novice clinicians or by experienced
clinicians when confronted with diagnostic dilemmas
• Slow process, less susceptible to bias
• Explicit, based on knowledge and logic
• Requires considerable cognitive work
System 2: The Analytical Approach
Example:
“Possible etiologies of chorea include metabolic
disorders, nutritional deficiencies, infections,
immune-mediated disorders, vascular ischemia,
toxins and medication side effects.”

9. Clinical Teaching Point
Chorea
• An uncommon symptom, especially in older adults
• Hyperkinetic movement disorder
• Rapid, semi-purposeful, non-patterned involuntary
movements involving distal or proximal muscle groups
• video: http://www.edge-
cdn.net/video_900389?playerskin=37016

10. Clinical Teaching Points
Differential Diagnosis for Chorea
Acquired Hereditary
System 1 Infectious
• Acute rheumatic fever
Huntington Disease
Wilson Disease
System 2 Infectious
• CNS, HIV-associated, neurosyphilis
Spinocerebellar ataxias
Malignancy
• Paraneoplastic
Neuroacanthocytosis
Toxins/Deficiencies
• Heavy metal toxicity, B12 deficiency
Hepatocellular degeneration
Drug-associated
• Metoclopramide, prochlorperazine
Immune-mediated
• SLE, anti-phospholipid syndrome, celiac
disease, sarcoidosis
Vascular
• Basal ganglia stroke

11. More HistoryMore History
Medications
• Atorvastatin
• Digoxin
• Furosemide
• Levothyroxine
• Vitamin B12
• Warfarin
Family History
• No known history of
neurodegenerative disease
or malignancy
PMH
• Afib
• HTN
• Hypothyroidism
• Vitamin B12 deficiency
Social History
• Widowed
• 30 pack-year history of
tobacco use, quit 6
months ago
• No alcohol or illicit drug
use

12. Physical Exam
T 98.6 °F BP 108/62 HR 114 Sat 97% RA
• General: cachectic, chronically ill appearing, in no
distress. Alert and oriented
• CV: heart rhythm irregularly irregular, no murmur
• Pulmonary, gastrointestinal and integumentary systems
normal

13. Physical Exam cont’d: Neurological Exam
• Mental Status: Alert and oriented to name, place, date
• Cranial Nerves: Oral dyskinesias and severe dysarthria.
• Motor: moderate generalized muscle atrophy consistent
with cachexia and paratonia in both upper extremities
(involuntary variable resistance during passive movement).
Choreiform movements in upper extremities. 4/5 strength in
all extremities.
• Sensory: decreased vibratory sensation below both knees.
• Reflexes: 1+ in upper extremities, absent in lower
extremities. Flexor plantar responses.
• Coordination: finger-to-nose task impaired due to upper
extremity chorea
• Gait: not tested as patient unable to stand.

14. Discussion
What studies do you want and why?

15. CT head/chest/abdomen/pelvis with and without contrast
No significant findings
Labs and Additional Studies
TSH: normal
INR: 2.3
electrolytes normal CBC normal
Electromyelogram
Mild distal motor neuropathy

16. Additional Imaging
MRI brain
T1 hyperintensity within
the basal ganglia with
thalamic sparing.
No areas of ischemia
or hemorrhage.

17. Discussion
Based on this new information, what is your problem
representation* for this patient?
Use your problem representation to refine your
differential diagnosis.
Are you using intuitive (System 1) or analytical (System 2)
reasoning?
What would you do next?
*Problem representation: a summary sentence that highlights the defining
features of a case

18. Case Continued
• Neurology was consulted. The constellation of
abnormal neurologic exam findings, hyperintensity of
the basal ganglia, and normal labs raised suspicion
for a paraneoplastic neurologic syndrome.
• Paraneoplastic antibody tests were performed and
returned positive for anti-CRMP-5 IgG at a level of
1:3,840 (normal < 1:240).
• Malignancy has been reported in greater than 90% of
cases with anti-CRMP-5 antibody.

19. Case Continued
Malignancy evaluation negative
• CT C/A/P
• Mammogram
• Colonoscopy
3 months later
• CRMP-5 Ab repeated, again positive
Patient referred to Oncology
• PET scan showed 1.5cm hypermetabolic lymph node posterior to
trachea
EUS-guided FNA positive for malignant cells
• Stained positive for synaptophysin and TTF-1
Pathology confirmed small cell cancer of
pulmonary origin

20. Patient Outcome
• Patient underwent 4 cycles of chemotherapy,
lung radiation therapy and prophylactic whole
brain radiation therapy.
• One year following treatment, she had gained
weight, was eating well, and was no longer
wheelchair-bound.
• Most recent CRMP-5 antibody titer was
negative.

21. Recap: Dual Process Theory
• Dual Process Theory describes how expert
clinicians think.
• System 1 is fast and relies on pattern recognition,
while System 2 is slower and relies on an effortful
attempt to organize and structure knowledge.
• Incorporating Dual Process Theory into clinical
problem-solving helps clinicians consciously slow
down and avoid cognitive biases when faced with
diagnostic dilemmas.

22. Teaching Point
• Underlying malignancy with paraneoplastic
syndromes should be considered for patients with
clinical syndromes that do not fit with common
illness scripts.
• The CRMP-5 antibody can produce chorea and
seems to be associated with malignancy in greater
than 90% of cases.

23. Acknowledgements
• Teaching slides are based on: Vick A, Kraemer RR,
Morris JL, Willett LL, Centor RM, Estrada CA,
Rodriguez JM. A 60-Year-Old Woman with Chorea
and Weight Loss. J Gen Intern Med.
2012;27(6):747-51.
• This work, assisted by editorial group Drs.
Carlos Estrada, Amanda Vick and Jeff Kohlwes, is
licensed under a Creative Commons Attribution-
NonCommercial-ShareAlike 4.0 International
License

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